Top D Nicholas, Stephenson Kevin G, Doxey Christopher R, Crowley Michael J, Kirwan C Brock, South Mikle
Brigham Young University, Provo, Utah.
Yale Child Study Center, New Haven, Connecticut.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2016 Jul;1(4):308-315. doi: 10.1016/j.bpsc.2016.01.008. Epub 2016 Feb 11.
Anxiety is the most common comorbid psychiatric concern in individuals diagnosed with autism spectrum disorder (ASD) and can cause significant functional impairment. Fear conditioning tasks offer a useful neurodevelopmental model for anxiety, yet there are no published neuroimaging studies of fear conditioning using ASD samples.
Twenty adults diagnosed with ASD and 19 healthy adult control subjects completed a standard fear conditioning and extinction paradigm while undergoing functional magnetic resonance imaging scanning. A burst of air on the base of the neck was the unconditioned stimulus. Participants returned 1 day later for scanning during an extinction recall phase. A priori regions of interest were analyzed with a familywise error correction rate < 0.05.
All regions of interest demonstrated significantly greater response to threat than safe conditions during initial fear acquisition. Compared with age-matched control subjects, the ASD group showed a significantly decreased differential response to threat versus safe cues in right amygdala during the initial fear acquisition phase and decreased response in left amygdala during the first run of extinction recall on the second day of scanning.
Symptoms of severe anxiety in ASD may arise from atypical neural mechanisms especially related to the differentiation of threat versus safe cues. An inability to effectively identify safety contexts may underlie chronically increased levels of anxiety in many individuals diagnosed with ASD.
焦虑是被诊断为自闭症谱系障碍（ASD）的个体中最常见的共病精神问题，可导致显著的功能损害。恐惧条件化任务为焦虑提供了一种有用的神经发育模型，但尚无使用ASD样本进行恐惧条件化的神经影像学研究发表。
20名被诊断为ASD的成年人和19名健康成年对照者在进行功能磁共振成像扫描时完成了标准的恐惧条件化和消退范式。颈部基部的一阵气流作为无条件刺激。参与者在1天后返回进行消退回忆阶段的扫描。使用家族性错误校正率<0.05对先验感兴趣区域进行分析。
在初始恐惧习得期间，所有感兴趣区域对威胁的反应均显著大于对安全条件的反应。与年龄匹配的对照者相比，ASD组在初始恐惧习得阶段右侧杏仁核中对威胁与安全线索的差异反应显著降低，在扫描第二天的首次消退回忆中左侧杏仁核的反应降低。
ASD中严重焦虑症状可能源于非典型神经机制，尤其是与威胁与安全线索的区分有关。无法有效识别安全情境可能是许多被诊断为ASD的个体焦虑水平长期升高的基础。
